Changde Cheng

Contact

Stem Cell Biology Program
Division of Hematology and Oncology
Institute for Cancer Outcomes and Survivorship
Department of Biomedical Informatics and Data Science
O’Neal Comprehensive Cancer Center
Department of Medicine, Heersink School of Medicine
University of Alabama at Birmingham, USA

Wallace Tumor Institute 520A.
1824 6th Ave S Birmingham, Alabama 35233.

Email: ccheng [at] uabmc [dot] edu

Research Overview

We use high-dimensional genomic approaches to elucidate the molecular mechanisms underlying cancer progression and therapeutic resistance. Through integrated analysis of single-cell transcriptomics, spatial genomics, and multi-modal omics data, we systematically characterize cellular subpopulations and microenvironmental factors that contribute to disease origin, recurrence and resistance.

• High-Throughput Genomic Analysis
  • Single-cell RNA sequencing for cellular heterogeneity profiling
  • Spatial transcriptomics for microenvironmental context
  • Multi-modal omics integration for comprehensive molecular characterization
  • Perturbation-based functional genomics
• Computational Biology Applications
  • Development of robust statistical frameworks
  • Algorithm optimization for cellular state inference
• Theoretical Foundations
  • Population genetics
  • Quantitative genetics and phenotypic variation
  • Systematic analysis of evolutionary forces

Research Themes

My research focus evolves over time, starting with extensive work in ecological genomics and infectious disease vectors (2009-2014), centering on evolutionary genetics, theoretical biology, and computational genomics (from 2014), and most recently focusing on clinical applications in cardiac arrest, sepsis, and cancer biology (from 2023).

Immunological Mechanisms in Cardiac Arrest (since 2023)

Papers 25°, 28°, 31°

31°. Innate T cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation

Tomoyoshi Tamura\(^{\ast}\), Changde Cheng \(^{\ast}\), Ana Villaseñor-Altamirano\(^{\ast}\), Kei Hayashida, Kohei Ikeda\(^{\ast}\), Kohei Yamada\(^{\ast}\), Jaivardhan A Menon, Louis T. Merriam, Jack Varon, Jiyoung Choi, Aidan M. Cullen, Jingyu Guo, Benjamin A. Olenchock, Mayra A. Pinilla-Vera, Reshmi Manandhar, Muhammad Dawood Amir Sheikh, Peter C. Hou, Patrick R. Lawler, William M. Oldham, Raghu R. Seethala, Immunology of Cardiac Arrest Network (I-CAN), Rebecca M. Baron, Erin A. Bohula, David A. Morrow, Alexandra Weissman, Michael B. Brenner, Xiang Chen \(^{\dagger}\), Fumito Ichinose \(^{\dagger}\), Edy Y. Kim \(^{\dagger}\) .
Science Translational Medicine 2024 Dec 4; (16) 776.

• Best Abstract – The American Heart Association’s (AHA) Scientific Sessions 2024

28°. Protocol for immunophenotyping out-of-hospital cardiac arrest patients

Yamada K\(^{\dagger}\), Menon JA, Kim Y, Changde Cheng, Chen W, Shih JA, Villasenor-Altamirano AB, Chen X, Immunology of Cardiac Arrest Network (I-CAN), Tamura T, Merriam LT, Kim EY\(^{\dagger}\), Weissman AJ\(^{\dagger}\).
STAR Protocols 2024 Mar 15; 5 (1), 102874.

25°. Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Tamura T\(^{\ast}\), Changde Cheng \(^{\ast}\), Chen W, Merriam LT, Athar H, Kim YH, Manandhar R, Amir Sheikh MD, Pinilla-Vera M, Varon J, Hou PC, Lawler PR, Oldham WM, Seethala RR, Tesfaigzi Y, Weissman AJ, Baron RM, Ichinose F, Berg KM, Bohula EA, Morrow DA, Chen X, Kim EY.
Med. 2023 Jul 14;4(7):432-456.e6.

• immune response and inflammation after cardiac arrest
  • single-cell transcriptomics,
  • immune checkpoint regulation,
  • inflammation markers

Notable paper: 31°, the latest Science Translational Medicine publication (2024) on T cells.

Cancer Genomics, Stem Cell Biology, Therapeutic Response, Survival, and Outcome (since 2023)

Submissions № 2-10

№ 2. Transcriptome alteration in pancreatic neuroendocrine tumors among those living with adverse SDOH.

Andrea Gillis\(^{\ast}\), K. Kerrick Akinola\(^{\ast}\), Brendon Herring, Isra Elhussin, Elquis Castillo, Stuart Phipps, Vinodh Srinivasasainagendra, Weisheng Chen, Rachael Guenter, Tiwari Hemant, Doug Welsch, Dai Chen, Upender Manne, Herbert Chen, Clayton Yates, J Bart Rose, Changde Cheng, Smita Bhatia.
Submitted.

№ 3. Analysis of alternative mRNA splicing in anthracycline-induced cardiomyopathy – a COG-ALTE03N1 report.

Purnima Singh \(^{\ast}\), David K. Crossman \(^{\ast}\), Changde Cheng, Patrick J. Trainor, Noha Sharafeldin, Xuexia Wang, Liting Zhou, Lindsey Hageman, Saro H. Armenian, Frank M. Balis, Douglas S. Hawkins, Frank G. Keller, Melissa M. Hudson, Joseph P. Neglia, A. Kim Ritchey, Jill P. Ginsberg, Wendy Landier, Smita Bhatia.
Submitted.

№ 4. Paricalcitol and Hydroxychloroquine modulate extracellular matrix and enhance chemotherapy efficacy in pancreatic cancer.

Dhana Sekhar Reddy Bandi, Sujith Sarvesh, Jeremy Foote, Doug Welsch, Changde Cheng, Mehmet Akce, Ganji Purnachandra Nagaraju, Bassel F. El-Raye.
Submitted.

№ 5. Antibody deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.

Foote JB \(^{\dagger}\), Sarvesh S, Al Diffalha S, Crossman DK, Changde Cheng, Kim M, Rose BJ, Klug CA.
Submitted.

№ 6. Unraveling the clinical impact of differential DNA methylation in PDAC: A Systematic Review.

Raj Roy, Christopher Wu, Lauren Wheeler, K. Kerrick Akinola, Herbert Chen, J. Bart Rose, Changde Cheng, Smita Bhatia, Andrea Gillis
Submitted.

№ 7. Germline Pathogenic/ Likely Pathogenic Mutations and Subsequent Neoplasms among Childhood Cancer Survivors – A report from the Children’s Oncology Group ALTE03N1 Study.

RLiting Zhou , Purnima Singh , David K. Crossman , Joshua Richman , Mr Patrick J Trainor , Changde Cheng , Xuexia Wang , Noha Sharafeldin , Lindsey Hageman , Maryam Sheikh , Melissa Richard , Danielle N. Friedman , Joseph Neglia , Zhaoming Wang , Melissa M Hudson , Saro H Armenian , Douglas Hawkins , Ravi Bhatia , Wendy Landier, Smita Bhatia
Submitted.

№ 8. Acute myeloid leukemia microenvironment impairs neutrophil maturation and function through NFκB signaling.

Paran Goel, Sajesan Aryal, Alana M. Franceski, Valeriya Kuznetsova, Amanda Costa, Francesca Luca, Ashley N. Connelly, Daniel W. Phillips, Caroline C. Ennis, Sourajeet Karfa, Brittany L. Crown, Estelle Carminita, Virginia Camacho, Gracie M. Jack, Doug Welsch, Changde Cheng, Asumi Yokota, Rui Lu , Ravi Bhatia , Pran K. Datta, Kellie R. Machlus, P. Brent Ferrell , Hideyo Hirai and Robert S. Welner
Submitted.

№ 9. Clonal hematopoiesis and subsequent venous thromboembolism among survivors of autologous transplantation for lymphoma.
Radhika Gangaraju; Yanjun Chen; Lindsey Hageman; Alysia Bosworth; Elizabeth Ross; Liton Francisco; Purnima Singh; Melissa Richard; Chengcheng Yan; Rashi Kalra; Changde Cheng; Saro Armenian; Stephen Forman; Ravi Bhatia; Smita Bhatia.
Submitted.

№ 10. Marrow Minded: Characterizing Differences between Calvarium and Femur Bone Marrow Microenvironment in Diabetes.
Ashley Rennhack, Micheli Sielski, Bright Asare-Bediako, , Emory Johnson, Fadeela Sheini, Sergio Li Calzi, Changde Cheng, Maria B. Grant.
Submitted.

Papers 23°, 24°, 27°, 29°, 30°, 32°

32°. DNA damage response and repair genes and Anthracycline-induced cardiomyopathy in childhood cancer survivors: a report from the Children’s Oncology Group and the Childhood Cancer Survivor Study.

Xuexia Wang\(^{\ast}\), Purnima Singh\(^{\ast}\), Romina Cejas, Liting Zhou, Noha Sharafeldin, Patrick Trainor, Wendy Landier, Changde Cheng, Lindsey Hageman, Fan Wang, Yadav Sapkota, Yutaka Yasui, Melissa Hudson, Eric Chow, Saro Armenian, Joseph Neglia, Douglas Hawkins, Jill Ginsberg, Paul Burridge, Gregory Armstrong, and Smita Bhatia.
Circulation: Genomic and Precision Medicine, accepted.

30°. Epigenetic regulation of non-canonical menin targets modulates menin inhibitor response in acute myeloid leukemia

Xinyue Zhou, Lixia Zhang, Sajesan Aryal, Virginia Veasey, Amanda Tajik, Cecilia Restelli, Steven Moreira, Pengcheng Zhang, Yanfeng Zhang, Kristin Hope, Yang Zhou, Changde Cheng, Ravi Bhatia, and Rui Lu.
Blood 2024 Nov 7; 144 (19): 2018–2032.

• Broken brakes: PRC loss foils menin inhibition – Commentary in Blood

29°. Sex-based differences in risk for therapy-related myeloid neoplasms

Melissa A Richard\(^{\ast}\), Chengcheng Yan\(^{\ast}\), Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman , Smita Bhatia\(^{\dagger}\), Ravi Bhatia\(^{\dagger}\)
Journal of Clinical Oncology 2024 Nov 1; Vol. 42, No 31.

• Battle of the sexes in the clonal world – Editorials in JCO

27°. Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q

Murphy AJ\(^{\ast \dagger}\), Changde Cheng \(^{\ast}\), Williams J, Shaw TI, Pinto EM, Dieseldorff-Jones K, Brzezinski J, Renfro LA, Tornwall B, Huff V, Hong AL, Mullen EA, Crompton B, Dome JS, Fernandez CV, Geller JI, Ehrlich PF, Mulder H, Oak N, Maciezsek J, Jablonowski C, Fleming AM, Pichavaram P, Morton CL, Easton J, Nichols KE, Clay MR, Santiago T, Zhang J, Yang J, Zambetti GP, Wang Z, Davidoff AM, Chen X \(^{\dagger}\).
Nat Commun. 2023 Dec 18; 14, 8006.

24°. Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma

Fang J\(^{\ast}\), Singh S\(^{\ast}\), Changde Cheng \(^{\ast}\), Natarajan S\(^{\ast}\), Sheppard H\(^{\ast}\), Abu-Zaid A, Durbin AD, Lee HW, Wu Q, Steele J, Connelly JP, Jin H, Chen W, Fan Y, Pruett-Miller SM, Rehg JE, Koo SC, Santiago T, Emmons J, Cairo S, Wang R, Glazer ES, Murphy AJ, Chen T, Davidoff AM, Armengol C, Easton J, Chen X, Yang J.
Nat Commun. 2023 Jul 6;14(1):4003.

• Spatial omics takes off – St. Jude Progress
  Our work serves as a key example of leveraging spatial transcriptomics to uncover the heterogeneity of hepatoblastoma tumors and to illuminate their responses to different therapeutic interventions.

23°. Identification and targeting of a HES1-YAP1-CDKN1C functional interaction in fusion-negative rhabdomyosarcoma

Kovach AR, Oristian KM, Kirsch DG, Bentley RC, Changde Cheng, Chen X, Chen PH, Chi JA, Linardic CM.
Mol Oncol. 2022 Oct;16(20):3587-3605.

• Research Themes:
  • Wilms tumor genetics and epigenetics
  • Hepatoblastoma genomics and drug response
  • Pancreatic cancer tumorigeneiss and chemotherapy
  • Leukemia treatment (menin inhibitor response)
  • Therapy-related myeloid neoplasms
  • Rhabdomyosarcoma biology

Computational Biology and Single-Cell Analysis (since 2019)

Papers 19°, 26°

26°. A review of single-cell rna-seq annotation, integration, and cell-cell communication

Changde Cheng \(^{\ast}\), Chen W\(^{\ast}\), Jin H\(^{\ast}\), Chen X.
Cells. 2023 Jul 30;12(15). Review.

19°. Latent cellular analysis robustly reveals subtle diversity in large-scale single-cell RNA-seq data

Changde Cheng, Easton J, Rosencrance C, Li Y, Ju B, Williams J, Mulder HL, Pang Y, Chen W, Chen X.
Nucleic Acids Res. 2019 Dec 16;47(22):e143.

• Benchmarking clustering algorithms on estimating the number of cell types from single-cell RNA-sequencing data – Researchers at the University of Sydney ranked our scLCA among the leading methods for accurate cell type number estimation in single-cell RNA sequencing analysis: “one of the top-performing methods on the number of cell type estimation …”

• Focus on computational methods for:
  • Single-cell RNA sequencing analysis
  • Cell annotation and integration
  • Cell-cell communication analysis

Evolutionary Biology, Genetics, and Theory (since 2016)

Submission № 1

№ 1. Sexually antagonistic selection and sex chromosome evolution in Stickleback.
Changde Cheng, Andrius J. Dagilis, Jason M. Sardell, Asano Ishikawa, Jun Kitano, Matthew P. Josephson, Catherine L. Peichel, Mark Kirkpatrick.
Submission to the 2017 Society for Molecular Biology & Evolution meeting at Austin, Texas, US.

Papers 11°, 16°, 17°, 20°-22°

22°. Molecular evolution and the decline of purifying selection with age

Changde Cheng, Kirkpatrick M.
Nat Commun. 2021 May 11;12(1):2657.

21°. Predicting the evolution of sexual dimorphism in gene expression

Houle D, Changde Cheng.
Mol Biol Evol. 2021 May 4;38(5):1847-1859.

20°. Predicting multivariate responses of sexual dimorphism to direct and indirect selection

Changde Cheng, Houle D.
Am Nat. 2020 Oct;196(4):391-405.

17°. Inversions are bigger on the X chromosome

Changde Cheng, Kirkpatrick M.
Mol Ecol. 2019 Mar;28(6):1238-1245.

16°. Systems genetic analysis of inversion polymorphisms in the malaria mosquito Anopheles gambiae

Changde Cheng, Tan JC, Hahn MW, Besansky NJ.
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7005-E7014.

11°. Sex-Specific selection and sex-biased gene expression in humans and flies

Changde Cheng, Kirkpatrick M.
PLoS Genet. 2016 Sep;12(9):e1006170.

• Research Themes:
  • Molecular evolution and aging
  • Sexual dimorphism
  • Chromosomal inversions, local adaptation, and speciation
  • Sex-specific selection

Ecological/Evolutionary Genomics and Infectious Disease (since 2009)

Papers 1°-10°, 12°

12°. Extensive genetic differentiation between homomorphic sex chromosomes in the sosquito vector, Aedes aegypti

Fontaine A, Filipovic I, Fansiri T, Hoffmann AA, Changde Cheng, Kirkpatrick M, Rašic G, Lambrechts L.
Genome Biol Evol. 2017 Sep 1;9(9):2322-2335.

10°. Transcriptomic differences between euryhaline and stenohaline malaria vector sibling species in response to salinity stress

Uyhelji HA, Changde Cheng, Besansky NJ.
Mol Ecol. 2016 May;25(10):2210-25.

9°. Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes

Hall AB\(^{\ast}\), Papathanos PA\(^{\ast}\), Sharma A\(^{\ast}\), Changde Cheng \(^{\ast}\), Akbari OS, Assour L, Bergman NH, Cagnetti A, Crisanti A, Dottorini T, Fiorentini E, Galizi R, Hnath J, Jiang X, Koren S, Nolan T, Radune D, Sharakhova MV, Steele A, Timoshevskiy VA, Windbichler N, Zhang S, Hahn MW, Phillippy AM, Emrich SJ, Sharakhov IV, Tu ZJ, Besansky NJ.
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2114-23.

8°. Genome-wide QTL mapping of saltwater tolerance in sibling species of Anopheles (malaria vector) mosquitoes

Smith HA, White BJ, Kundert P, Changde Cheng, Romero-Severson J, Andolfatto P, Besansky NJ.
Heredity (Edinb). 2015 Nov;115(5):471-9.

7°. Gene expression divergence between malaria vector sibling species Anopheles gambiae and An. coluzzii from rural and urban Yaoundé Cameroon

Cassone BJ, Kamdem C, Changde Cheng, Tan JC, Hahn MW, Costantini C, Besansky NJ.
Mol Ecol. 2014 May;23(9):2242-59.

6°. Cuticular differences associated with aridity acclimation in African malaria vectors carrying alternative arrangements of inversion 2La

Reidenbach KR, Changde Cheng, Liu F, Liu C, Besansky NJ, Syed Z.
Parasit Vectors. 2014 Apr 10;7:176.

5°. Ecological genomics of Anopheles gambiae along a latitudinal cline: a population-resequencing approach

Changde Cheng, White BJ, Kamdem C, Mockaitis K, Costantini C, Hahn MW, Besansky NJ.
Genetics. 2012 Apr;190(4):1417-32.

4°. Divergent transcriptional response to thermal stress by Anopheles gambiae larvae carrying alternative arrangements of inversion 2La

Cassone BJ, Molloy MJ, Changde Cheng, Tan JC, Hahn MW, Besansky NJ.
Mol Ecol. 2011 Jun;20(12):2567-80.

3°. Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium

White BJ, Lawniczak MK, Changde Cheng, Coulibaly MB, Wilson MD, Sagnon N, Costantini C, Simard F, Christophides GK, Besansky NJ.
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):244-9.

2°. Genetic association of physically unlinked islands of genomic divergence in incipient species of Anopheles gambiae

White BJ, Changde Cheng, Simard F, Costantini C, Besansky NJ.
Mol Ecol. 2010 Mar;19(5):925-39.

1°. The population genomics of trans-specific inversion polymorphisms in Anopheles gambiae

White BJ, Changde Cheng, Sangaré D, Lobo NF, Collins FH, Besansky NJ.
Genetics. 2009 Sep;183(1):275-88.

• Research Themes:
  • African malaria mosquito Anopheles gambiae genetics
  • Malaria vector studies
  • Y chromosome evolution
  • Chromosomal rearrangements
  • Local adaptation and speciation
  • Population genomics

Plant Biology (2019)

Paper 18°

18°. Complex interactions between day length and diurnal patterns of gene expression drive photoperiodic responses in a perennial C(4) grass

Weng X, Lovell JT, Schwartz SL, Changde Cheng, Haque T, Zhang L, Razzaque S, Juenger TE.
Plant Cell Environ. 2019 Jul;42(7):2165-2182.

Focus on gene expression patterns in C4 grass related to photoperiod response

• Diurnal transcriptional profiling